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http://dx.doi.org/10.5352/JLS.2009.19.9.1209

Quercetin Potentiates TRAIL-induced Apoptosis in Human Colon KM12 Cells  

Park, Jun-Ik (Department of Biochemistry, Pusan National University School of Medicine)
Kim, Hak-Bong (Department of Biochemistry, Pusan National University School of Medicine)
Kim, Mi-Ju (Department of Biochemistry, Pusan National University School of Medicine)
Lee, Jae-Won (Department of Biochemistry, Pusan National University School of Medicine)
Bae, Jae-Ho (Department of Biochemistry, Pusan National University School of Medicine)
Park, Soo-Jung (Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health)
Kim, Dong-Wan (Department of Microbiology, College of Natural Sciences, Chang Won National University)
Kang, Chi-Dug (Department of Biochemistry, Pusan National University School of Medicine)
Kim, Sun-Hee (Department of Biochemistry, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.19, no.9, 2009 , pp. 1209-1217 More about this Journal
Abstract
Many cancer cells are sensitive to the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, some cancer cells show either partial or complete resistance to TRAIL. Human colon carcinoma KM12 cells have been shown to be insensitive to TRAIL-induced apoptosis. To overcome TRAIL resistance in KM12 cells, we targeted key anti-apoptotic molecules involved in the modulation of TRAIL resistance in the cells, and evaluated the effects of quercetin as a TRAIL sensitizer in the cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in KM12 cells by the down-regulation of c-FLIP and DNA-PKcs/Akt and up-regulation of death receptors (DR4/DR5), which led to the enhancement of TRAIL-mediated activation of caspases and subsequent cleavage of PARP, as well as up-regulation of Bax. These findings suggest that the DNA-PKcs/Akt signaling pathway, as well as c-FLIP, play essential roles in regulating cells in the escape from TRAIL-induced apoptosis. Based on these results, this study provides a potential application of quercetin in combination with TRAIL in the treatment of human colon cancer.
Keywords
TRAIL; quercetin; DNA-PK/Akt; c-FLIP; KM12 cells; caspase;
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